NGS in Lung Cancer – Choosing the Right Test
Aaron Tan, National Cancer Centre Singapore

There is an expanding list of therapeutically relevant biomarkers for lung cancer, and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is a commonly encountered problem. This has led to the increasing adoption of multiplexed assays, notably NGS of tumour tissue, to evaluate multiple biomarkers in a single workflow. In addition, the analysis of circulating tumour DNA with liquid biopsies has seen rapid uptake. Nevertheless, establishing the clinical validity, feasibility, and cost-effectiveness of NGS assays compared with single biomarker assays for molecular profiling is crucial. Numerous studies have now confirmed the cost-effectiveness for NGS in lung adenocarcinoma, including in Singapore. This is particularly relevant for Asian lung cancer populations, in which EGFR mutations are the predominant driver alteration. Healthcare resource utilisation, drug costs, and long-term patient outcomes need to be considered however, before implementation in different settings. Choosing the right NGS assay is also of critical importance. For many emerging biomarkers, there may not be established gold standard methods of detection. There may also be discordance between assays, for example RNA-based versus DNA-based NGS for MET exon 14 alterations. Notably the companion diagnostics for many recently US FDA approved targeted therapies have been panel-based NGS assays, including in tissue and plasma. This highlights the complexity of genomic profiling for lung cancer in contemporary clinical practice.